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Plasma Membrane

University of Arizona, Tucson, Arizona, USA Only a small fraction of the protein constituents of mitochondria are encoded in the small vestigial genome of the organelle. Most of the genes governing the biogenesis of mitochondria reside in the chromosomal DNA of the nucleus. Referred to as PET genes, they represent a sizeable fraction of the total genetic information in the nucleus. PET genes code for the enzymes making up the different metabolic pathways housed in mitochondria, for the...

Columbia University College of Physicians and Surgeons, New York, USA Neuronal intermediate filaments (IFs) are 10-12 nm filaments that are expressed in the nervous system. IF proteins belong to a large gene family and the expression of different IF proteins is tissue specific. In the nervous system, different neuronal IFs are expressed in neuroepithelial stem cells, the central nervous system (CNS) and peripheral nervous system (PNS). In addition, the expression patterns of these neuronal IFs...

AD is a neuro-degenerative disease characterized by the progressive deterioration of higher cognitive functions, including memory loss. Since nicotinic receptors play a critical role in learning and memory, it is not surprising that AD patients lose the cholinergic pathways from the basal forebrain to the hippocampus and the cortex. Moreover, the brains of AD patients have a reduced number of cholinergic cells and presynaptic nAChRs. Since low levels of ACh are believed to lead to the cognitive...

The NPY Y1 receptor is pharmacologically characterized by its high affinity for Pro34 NPY and D-Arg25 NPY its low affinity for N-terminally truncated NPY analogues and its high affinity for nonpeptide antagonists such as 1229U91, BIBP3226, and BIBO3304 (Table 1, Figure 1). Structurally, the receptor is related to the NPY Y4 and NPY y6 receptors (Figure 2). NPY Y1 receptor mRNA is expressed at highest levels in brain (especially cortex, hippocampus, thalamus, and hypothalamus), vascular smooth...

The ability of the neurotransmitter transporters to regulate normal synaptic signaling implies that functional modification of transporter activity might contribute to the etiology of multiple neurobiological diseases. Indeed, many studies have suggested for years, largely on the basis of pharmacology, that the monoamine transporters NET, DAT, and SERT play an important role in regulating mood, learning, and motor activity, while GABA transporters have been implicated in neuronal excitability...

Danzer, Oya Yazgan and Pamela K. Geyer University of Iowa, Iowa City, Iowa, USA Gene silencing is the process whereby a gene is inactivated due to its chromosomal position. Chromosomal rearrangements that move a gene from a transcriptionally permissive location to a transcriptionally nonpermissive location result in gene silencing. This loss of gene expression is not due to a mutation in a gene itself, but due to the placement of a gene into a chromatin environment...

The process of DNA non-homologous end joining (NHEJ) is one of several mechanisms that function to repair DNA double strand breaks (DSBs) in DNA. NHEJ represents the major mechanism for DSB repair in G1 phase cells. If unrepaired, a DSB can lead to loss of genomic material which is likely to result in cell death a misrepaired DSB can cause genomic rearrangements, a potential initiating event for carcinogenesis. NHEJ, therefore, represents an important mechanism for maintaining genomic...

In 1905 Otto Folin, carrying out experiments on himself and others, described how urea excretion fluctuated with dietary protein, in particular, he showed how it reached a minimum within two days of consuming a zero protein diet. Thus it is clear that flux through the cycle is highly regulated and as with many biochemical pathways, this involves both short-term (changes in enzyme activity with no change in the amount of enzyme) and long-term (changes in the amount of enzyme) mechanisms. The...

The ligand selectivity for NPR-A is ANP &gt BNP q CNP, whereas the ligand selectivity for NPR-B is CNP q ANP &gt BNP. Mice lacking NPR-A are hypertensive and develop cardiac hypertrophy and ventricular fibrosis. In addition, they are completely unresponsive to the renal and vasorelaxing effects of ANP and BNP, consistent with NPR-A being the sole signaling receptor for these peptides. A promoter mutation resulting in reduced transcription of the human NPR-A gene was recently identified and...

Osaka Bioscience Institute, Suita, Osaka, Japan Oxygenases are a group of oxidative enzymes that catalyze the direct addition or fixation of molecular oxygen into various substrates. The terms mono and di oxygenases are generally assigned to the enzymes catalyzing the incorporation of either one or two atoms of oxygen per mole of substrate, respectively. Prior to the discovery of oxygenases in 1955, the essential characteristics of biological oxidation processes was believed to be the removal...

Increasing evidence demonstrates that proNT and NTS1 are deregulated in several human cancers such as colon, pancreatic, prostate, and lung cancer, suggesting that NT may exert an autocrine activation of its own NTS1 receptor in cancer. Thus, the use of NT receptor antagonists to block the proliferative effect of NT on cancer cells is one of the promising prospects in cancer therapy. In this respect, it has been recently reported that SR 48692 could inhibit NT-stimulated growth of human colon,...

Australian National University, Canberra, Australia In this article the oxidative and non-oxidative segments of the pentose pathway (PP) of glucose metabolism are defined. The discovery in 1931-1935 by the German biochemist, Otto Warburg, of the oxidative division of the pathway and of the chemistry and role of a new pyridine nucleotide co-enzyme in its reactions is deliniated. The successful revelation of many of the reactants and enzymes of the non-oxidative PP was largely achieved by two...

Neurotensin and Dopamine Interaction More than twenty years ago, it was observed that some behavioral and biochemical effects of centrally administered NT were similar to those exhibited by antipsycho-tic drugs, and that these drugs stimulated NT expression in brain regions where there are mesocorticolimbic and nigrostriatal DA neuronal projections. These observations led to the hypothesis that NT may act as an endogenous neuroleptic, and stimulated the research on NT-DA interactions. Moreover,...

This family of enzymes phosphorylates a series of seryl residues in the C-terminus of S6. It was identified in the 1980s following early work showing that insulin, and a range of other stimuli, led to increased phosphorylation of S6. The p70 S6 kinases were some of the earliest insulin- and mitogen-stimulated kinases to be studied in any detail, largely because the relatively high abundance of S6 means that it appears as a major insulin-stimulated phosphoprotein. p70 S6 kinases are now believed...

Rutgers University, New Brunswick, New Jersey, USA The ornithine cycle, also known as the urea cycle and the Krebs-Henseleit cycle, is the pathway in mammalian liver that allows the detoxification and excretion of excess nitrogen as urea. Flux through the cycle is driven by the demand to remove excess ammonia derived from the degradation of amino acids that arise either from the diet or from endogenous proteolysis. In a healthy individual, consuming a typical western diet, flux through the...

The first natriuretic peptide to be identified was atrial natriuretic peptide (ANP), which was originally called atrial natriuretic factor (ANF) because of its unknown structure. It was discovered by de Bold and co-workers in 1981. They found that intravenous infusion of atrial, but not ventricular, homogenates into rats caused a rapid and dramatic increase in renal sodium and water excretion that was accompanied by reduced blood pressure. Subsequently, a smooth muscle relaxing activity was...